Gene regulation in Streptococcus pneumoniae - RePub - Erasmus ...

Chapter 3
Abstract
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Previous studies have indicated that PsaR of Streptococcus pneumoniae is a
manganese-dependent regulator, negatively affecting the expression of at least seven genes.
Here, we extended these observations by transcriptome and proteome analysis of psaR
mutants in strains D39 and TIGR4. The microarray analysis identified three shared PsaR
targets: the psa-operon, pcpA, and prtA. Additionally, we found 31 genes to be regulated by
PsaR in D39 only, most strikingly a cellobiose-specific PTS and a putative bacteriocin operon
(sp0142-sp0146). In TIGR4, 14 PsaR gene targets were detected, with the rlrA pathogenicity
islet being the most pronounced. Proteomics confirmed most of the shared gene targets. To
examine the contribution of PsaR to pneumococcal virulence, we compared D39 and TIGR4
wild-type (wt) and psaR-mutants in three murine infection models. During colonization, no
clear effect was observed of the psaR mutation in either D39 or TIGR4. In the pneumonia
model, small but significant differences were observed in the lungs of mice infected with
either D39wt or ∆psaR: D39∆psaR had an initial advantage in survival in the lungs.
Conversely, TIGR4∆psaR-infected mice had significantly lower bacterial loads at 24h only.
Finally, during experimental bacteremia, D39∆psaR-infected mice had significantly lower
bacterial loads in the blood stream than wt-infected mice for the first 24h of infection.
TIGR4∆psaR showed attenuation at 36h only. In conclusion, our results show that PsaR of
D39 and TIGR4 has a strain-specific role in global gene expression and in the development of
bacteremia in mice.